Retinitis pigmentosa (RP) is a debilitating eye disease that affects 1 in 3,000 people in Australia. RP11 is a type of RP most commonly caused by a mutation in the PRPF31 gene. RP11 is dominantly inherited, meaning that only one copy of the gene with a mutation is required to cause disease and it is estimated to account for 250 cases in Australia. There is no treatment available to patients burdened with this condition. Given the recent development of gene-based therapy to treat PRPF31 disease, we sought to find families with PRPF31-associated RP by performing a gene panel testing on 40 families presenting with a dominant pedigree.
Project Results and Impact
A total of 40 dominant RP families were analysed and 23 (58%) returned a positive or likely positive result. Amongst the remaining 17 (42%) families with inconclusive results, further analysis was undertaken to resolve 9 of these families, identifying PRPF31 (n=3), PRPF6, SAG, RPE65, IMPG1, IMPDH1, and BEST1as causative genes. This left 8 (20%) dominant RP pedigrees unresolved. Additional analysis is now underway in these 8 unresolved families to find new mutations and new genes causing dominant RP.
Overall we found that the PRPF31 and RHO genes are the most common causes of dominant RP in Australia. PRPF31 mutations can be missed without specific analysis for large deletions in the gene. In total, 13 different genetic diseases were found in 40 families with dominant RP. Many of these genes can manifest in other forms of inherited retinal disease aside from RP and may also have recessive inheritance.
In conclusion, the success rate of gene panel testing can be improved from 58% to 80% with the independent variant curation, additional testing for large deletions and familial phase testing.
This project was featured in one of Retina Australia’s 2022 webinars. You can view a recording of the event here.
Associate Professor Fred K Chen
Centre for Ophthalmology and Visual Sciences, The University of Western Australia
Professor Sue Fletcher, Harry Perkins Institute of Medical Research, Perth
Dr Tina Lamey, Sir Charles Gairdner Hospital, Perth
Laura Florez, PYC Therapeutics, Perth